Sjogren's syndrome is said to be an autoimmune disease whose cardinal manifestation is a sicca syndrome associated with keratoconjunctivitis sicca and chronic sialadenitis but the mechanisms of its onset remain to be elucidated.
Diagnosed as Sjogren's syndrome is either a glandular (primary) syndrome which is confined to the lacrimal and salivary glands and clinically characterized by the so-called dry eye/dry mouth symptom or an extraglandular (secondary) syndrome characterized by a broad spectrum of generalized symptoms involving the liver, lung, thyroid gland, pancreas, kidney, and other organs. It is also known that the glandular syndrome progresses to the extraglandular syndrome in many cases and, though rarely, gives rise to malignant lymphoma.
As autoantibodies detected in Sjogren's syndrome, SS-A/Ro and SS-B/La are known. The corresponding antigens of these antibodies have already been identified but their specificity is low, with patients possessing autoantibodies to these antigens accounting for 40-60% of the total population of patients with Sjogren's syndrome. Moreover, in many cases SS-A/Ro- or SS-B/La-positive patients have complications such as systemic lupus erythematosus and rheumatism [Journal of Clinical Investigation, 87, p68-76, 1991; and Nucleic Acids Research, 17, p2233-2244, 1989].
In view of the above findings, those antibodies or antigens are regarded as indicators of all autoimmune diseases inclusive of Sjogren's syndrome. However, neither a specific autoantigen nor a specific autoantibody that could be a specific indicator of primary Sjogren's syndrome is not heretofore known.
.alpha.-Fodrin is one of subunits of fodrin which is a macromolecular actin-binding protein present immediately beneath the plasma membrane of cells. Fodrin forms high-order structures such as the fodrin network and is considered to be associated with the morphogenesis of cells and the migration of secretory granules to the surface membrane.
It has recently been reported that in programmed cell deaths such as apoptosis, the full-length .alpha.-fodrin of 240 K is restrictively cleaved by proteases to yield .alpha.-fodrin protein fragments [Journal of Biological Chemistry, 270, p6425-6428, 1995]. Moreover, as the proteases causing such restricted cleavage of .alpha.-fodrin, trypsin, chymotrypsin, and calpain are known [Journal of Neuroscience, 8, p.2640-2651, 1988].
However, the relationship of this restricted cleavage of .alpha.-fodrin to Sjogren's syndrome remains to be known.
Therefore, if an autoantibody or autoantigen specific to Sjogren's syndrome, particularly primary Sjogren's syndrome, is discovered, not only will the diagnosis of Sjogren's syndrome be faciliated and made more definite but the prophylaxis and therapy of Sjogren's syndrome, particularly primary Sjogren's syndrome, and, hence, prevention of progression of primary to secondary syndrome will be made possible by establishing a tolerance to autoantigens prior to onset of the disease or after the onset.
Furthermore, detailed analyses for elucidation of the mechanisms of onset of Sjogren's syndrome will also become feasible.